Low Dose ColchicinE in pAtients With Peripheral Artery DiseasE to Address Residual Vascular Risk

NCT04774159 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: LEADER-PAD
• Study Type: interventional
• Target: 6,150
• Locations: 9 countries
• Sites: 70

Brief Summary

The Low dose ColchicinE in pAtients with peripheral Artery DiseasE to address residual vascular Risk (LEADER-PAD) trial will evaluate if anti-inflammatory therapy with colchicine will reduce vascular events in patients with symptomatic peripheral artery disease.

Conditions

Peripheral Arterial Disease; Atherosclerosis of Extremities; Inflammation

Keywords

Acute limb ischemia; Myocardial Infarction; Stroke; Cardiovascular death; Mortality

Outcome Measures

Primary Outcomes (1)

• Major adverse cardiovascular and limb events (MACE or MALE)

  This composite outcome consists of cardiovascular deaths, myocardial infarction, stroke, and severe limb ischemia that requires a vascular intervention (i.e., pharmacological reperfusion, endovascular or surgical revascularization) or a major vascular amputation (defined as ankle/transtibial amputation or higher)

  3-5 years

Secondary Outcomes (14)

• Extended MALE

  3-5 years

• Cardiovascular death

  3-5 years

• Myocardial infarction

  3-5 years

• Stroke

  3-5 years

• Hospitalization

  3-5 years

Other Outcomes (8)

• Occurrence of gastrointestinal toxicity (such as diarrhoea, nausea or vomiting) that results in study drug discontinuation

  3-5 years

• Muscle pain (myalgia or myositis), that results in study drug discontinuation

  3-5 years

• Infection (e.g., pneumonia) leading to hospitalization

  3-5 years

Study Arms (2)

Colchicine

ACTIVE COMPARATOR

Colchicine 0.5mg daily for the duration of the trial

Drug: Colchicine 0.5 MG Oral Tablet

Colchicine-Placebo

PLACEBO COMPARATOR

Colchicine-Placebo daily

Drug: Colchicine-Placebo

Interventions

Colchicine 0.5 MG Oral Tablet DRUG

Colchicine 0.5 mg tablet daily Active drug and placebo are of the same appearance and are indistinguishable. All investigators, study personnel and patients will be blinded to drug treatment assignment. Trial treatment supplies must be stored in a secure, limited-access location under the storage conditions specified on the IP supply label.

Also known as: Colchicine

Colchicine

Colchicine-Placebo DRUG

Colchicine-Placebo tablet

Also known as: Colchicine-Placebo tablet

Colchicine-Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18 years
• Symptomatic atherosclerotic LE PAD fulfilling at least one of the following:
• a. Intermittent claudication with ankle/arm blood pressure ratio\* (ABI ≤ 0.90) or artery stenosis ≥ 50% plus one of i. \>1 vascular bed affected by atherosclerosis ii. Diabetes iii. Heart failure iv. Chronic kidney disease (eGFR \< 60 mL/min/1.73 m2)
• b. Rest pain (mostly in foot) OR necrosis of limb OR gangrene of limb (corresponding to either Fontaine stages 3 or 4 OR Rutherford Classification categories 4 to 6). All must have an ankle/arm blood pressure ratio\* (ABI ≤ 0.90) OR artery stenosis ≥ 50%.
• \* In cases of incompressible ankle arteries, the presence of toe pressure ≤ 60 mm Hg or toe-brachial index ≤ 0.70 is acceptable
• c. Revascularization defined as limb bypass surgery or endovascular revascularization procedures (irrespective of the specific device used), including percutaneous transluminal angioplasty/stent of iliac or infra-inguinal arteries or extra-anatomical bypass surgery
• d. Leg or foot amputation for arterial vascular indications
• Written or verbal informed consent from the patient

You may not qualify if:

• Contraindication to colchicine
• Long term requirement for colchicine for another clinical indication
• Active diarrhoea
• eGFR \< 30 mL/min/1.73 m2
• Cirrhosis or severe chronic liver disease
• Woman who is pregnant, or breast-feeding or of child-bearing potential not protected by reliable contraception or is planning conception during the study
• Current or planned long term use of cyclosporine, verapamil, HIV protease inhibitors, azole antifungals, or macrolide antibiotics (with the exception of azithromycin)
• Patients who are deemed unlikely to return for follow-up
• Patients with life expectancy \< 1 year

Sponsors & Collaborators

• Population Health Research Institute: lead

Study Sites (70)

Yale School of Medicine

New Haven, Connecticut, 06511, United States

RECRUITING

University of Florida - Gainesville

Gainesville, Florida, 32611, United States

RECRUITING

Tampa General Hospital

Tampa, Florida, 33606, United States

RECRUITING

University of Chicago Medical Center

Chicago, Illinois, 60615, United States

RECRUITING

Henry Ford Health System

Detroit, Michigan, 48202, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

Rutgers University

Newark, New Jersey, 07103, United States

RECRUITING

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

RECRUITING

Duke Regional Hospital

Durham, North Carolina, 27704, United States

RECRUITING

Duke University Medical Center

Durham, North Carolina, 27710, United States

RECRUITING

Duke Raleigh Hospital

Raleigh, North Carolina, 27609, United States

RECRUITING

Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

RECRUITING

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

RECRUITING

Southwest Family Medicine

Dallas, Texas, 75235, United States

RECRUITING

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

Texas Tech University Health Sciences

Lubbock, Texas, 79430, United States

RECRUITING

Sentara Norfolk General Hospital

Norfolk, Virginia, 23507, United States

RECRUITING

University of Washington Medical Center

Seattle, Washington, 98195, United States

RECRUITING

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

Sir Charles Gairdner Hospital

Perth, Western Australia, Australia

RECRUITING

Universitair Ziekenhuis Leuven

Leuven, Belgium

RECRUITING

Clínica Procárdio

Blumenau, Santa Catarina, Brazil

RECRUITING

Sociedade Hospitalar Angelina Caron

Campina Grande do Sul, Brazil

RECRUITING

Hospital Universitário (CoraCentro Pesquisa Clinica)

Canoas, Brazil

RECRUITING

Incore

Dois Vizinhos, Brazil

RECRUITING

Via Medica

Goiânia, Brazil

RECRUITING

Hospital Carlos Fernando Malzoni

Matão, Brazil

RECRUITING

Santa Casa de Misericórdia de Ponta Grossa

Ponta Grossa, Brazil

RECRUITING

Instituto de Cardiologia do Rio Grande do Sul

Porto Alegre, Brazil

RECRUITING

CPTEM - Centro de Pesquisa e Tecnologia Multidisciplinar

São Paulo, Brazil

RECRUITING

Hospital Alemão Oswaldo Cruz

São Paulo, Brazil

RECRUITING

University of Calgary, Peter Lougheed Centre Vascular Clinic

Calgary, Alberta, Canada

RECRUITING

University of Alberta, Mazankowski Heart Institute

Edmonton, Alberta, Canada

RECRUITING

Hamilton General Hospital

Hamilton, Ontario, L8L 2X2, Canada

RECRUITING

London Health Sciences Centre

London, Ontario, Canada

RECRUITING

Vascular Health Bronte

Oakville, Ontario, Canada

RECRUITING

Corcare Cardiovascular Research Inc.

Scarborough Village, Ontario, Canada

RECRUITING

Niagara Health System

St. Catharines, Ontario, Canada

RECRUITING

Sunnybrook Research Institute

Toronto, Ontario, Canada

RECRUITING

Toronto General Hospital

Toronto, Ontario, Canada

RECRUITING

CIUSSS du Nord-de-l'île-de-Montréal, Hôpital du Sacré-Cœur-de-Montréal

Montreal, Quebec, Canada

RECRUITING

Centre intégré de santé et de services sociaux du Bas-Saint-Laurent

Rimouski, Quebec, G5L 3N2, Canada

RECRUITING

Cardiolife

Quito, Pichincha, Ecuador

RECRUITING

Hospital de Especialidades de las Fuerzas Armadas N 1

Quito, Pichincha, Ecuador

RECRUITING

UniCarMeDr.D

Quito, Pichincha, Ecuador

RECRUITING

AMCOR

Quito, Ecuador

RECRUITING

Deventer Hospital

Deventer, Netherlands

RECRUITING

Slingeland Hospital

Doetinchem, Netherlands

RECRUITING

University Medical Center Groningen

Groningen, Netherlands

RECRUITING

University Medical Center Utrecht

Utrecht, Netherlands

RECRUITING

University Hospital Basel, Angiology

Basel, Switzerland

RECRUITING

Ospedale Regionale Bellinzona e Valli - Ente Ospedaliero Cantonale

Bellinzona, Switzerland

RECRUITING

HFR Fribourg

Fribourg, Switzerland

RECRUITING

Hôpitaux Universitaires de Genève

Geneva, Switzerland

RECRUITING

University Hospital Zurich, Clinic of Angiology

Zurich, Switzerland

RECRUITING

Royal Sussex County Hospital

Brighton, England, United Kingdom

RECRUITING

Southmead Hospital

Bristol, England, United Kingdom

RECRUITING

Kent and Canterbury Hospital

Canterbury, England, United Kingdom

RECRUITING

Derriford Hospital

Plymouth, England, United Kingdom

RECRUITING

Pinderfields Hospital

Wakefield, England, United Kingdom

RECRUITING

Royal Infirmary Edinburgh

Edinburgh, Scotland, United Kingdom

RECRUITING

Bradford Teaching Hospital

Bradford, United Kingdom

RECRUITING

Cambridge University Hospitals

Cambridge, United Kingdom

RECRUITING

Hull Royal Infirmary

Hull, United Kingdom

RECRUITING

The Leeds Teaching Hospital

Leeds, United Kingdom

RECRUITING

Glenfield Hospital

Leicester, United Kingdom

RECRUITING

St. George's University Hospitals

London, United Kingdom

RECRUITING

St. Thomas Hospital

London, United Kingdom

RECRUITING

Norfolk and Norwich University Hospitals

Norwich, United Kingdom

RECRUITING

University Hospital Southampton

Southampton, United Kingdom

RECRUITING

MeSH Terms

Conditions

Peripheral Arterial Disease; Inflammation; Myocardial Infarction; Stroke

Interventions

Colchicine; Tablets

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Myocardial Ischemia; Heart Diseases; Infarction; Ischemia; Necrosis; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Noel C Chan, MD

  Population Health Research Institute, Hamilton, Ontario, Canada

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Noel C Chan, MD

CONTACT

905-521-2100; Noel.Chan@TAARI.CA

Jessica Tyrwhitt

CONTACT

leaderpad@phri.ca

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blind and use of similarly active and placebo tablets.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 21, 2021
• First Posted: March 1, 2021
• Study Start: May 6, 2021
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: March 24, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CH (5); US (19); GB (15); CA (11); NL (4); BE (1); BR (10); EC (4); AU (1)